The goal of this project is to investigate antibacterial property and biocompatibility of a new class of bioresorbable alloys for musculoskeletal repair and reconstruction. Despite advanced sterile surgical techniques and antibiotics, periprosthetic infections (PPI) still occur, and they are clinically challenging to treat. Once infected, these implants often require surgical removal because systemic administration of antibiotics does not provide adequate local antibiotic concentration and is ineffective when a biofilm forms, which leads to prolonged morbidity and significant health care burden. Thus, antibacterial biocompatible bioresorbable alloys are needed to mitigate these problems to reduce secondary surgeries, patient discomfort, and health care costs. Magnesium (Mg) alloys represent a promising new class of bioresorbable metals, providing complementary properties that are absent in implants available today. Commercially available pure Mg degrades too fast and is mechanically too weak for the surgical needs, while commercial Mg alloys contain aluminum (Al) or rare earth (RE) elements that pose serious concerns of long-term toxicity. The PI has engineered a novel class of Mg alloy composed of biocompatible elements that provide slower degradation and greater mechanical strength. The objective of this project is to determine antibacterial property and biocompatibility of the new Mg alloys for potential implant applications, e.g., fixation plates, screws, pins, and K-wires. The central hypothesis is that alloying Mg rationally with zinc (Zn) and calcium (Ca) will induce desirable biological responses in vitro and in vivo. The desirable biological responses for musculoskeletal implant applications include enhanced bone cell functions and regeneration, and reduced bacterial adhesion and viability on the new alloys, thus preventing infection. The central hypothesis is established based on the PI's prior results and positive effects of Mg, Zn, and Ca as essential nutrients for bone repair and immune system health. This project is innovative because the alloy design integrates biological benefits into the materials science tetrahedron to achieve synergistic properties for preventing infection and improving healing. Further, the approach for creating infection-free implants is innovative because it does not rely on antibiotics, and reduce the emergence of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common osteomyelitis-inducing pathogenic bacterium. This project is significant because it will produce critical knowledge on antibacterial property of Mg-Zn-Ca alloys and their biocompatibility for musculoskeletal implant applications, and overcome the critical gap toward preclinical studies and clinical translation.

Public Health Relevance

This research is relevant to the missions and priorities of National Institute of Health that pertain to relieving health care burden caused by bone loss, infection, and loss of mobility. The novel antibacterial biocompatible bioresorbable alloys will address the clinically challenging complications associated with periprosthetic infections, thus eliminating secondary surgeries for removing the infected implants, and reducing patient suffering and heath care costs. This new alloy will attract significant interest from the medical implant/device industry for technology transfer and commercialization, which will lead to better musculoskeletal implants for bone fracture fixation, reconstruction of critical-sized bone defects, torn ligaments, and other applications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR069373-02
Application #
9251239
Study Section
Special Emphasis Panel (ZAR1-YL (M1))
Program Officer
Washabaugh, Charles H
Project Start
2016-04-01
Project End
2019-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2017
Total Cost
$62,134
Indirect Cost
$17,134
Name
University of California Riverside
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521